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Identification and enzyme studies of rare amino acid biosynthesis from Streptomyces cattleya
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dc.contributor.advisor | O'Hagan, David | |
dc.contributor.author | Chan, K. K. Jason | |
dc.coverage.spatial | xi, 253 | en_US |
dc.date.accessioned | 2014-02-27T15:11:51Z | |
dc.date.available | 2014-02-27T15:11:51Z | |
dc.date.issued | 2013 | |
dc.identifier | uk.bl.ethos.595614 | |
dc.identifier.uri | https://hdl.handle.net/10023/4478 | |
dc.description.abstract | This thesis is focussed on the biosynthesis of three toxins: fluoroacetate, 4-fluoro-L-theronine and β-ethynyl-L-serine which are biosynthesised by the soil bacteria Streptomyces cattleya. The two fluorinated metabolites originate from a common biosynthetic pathway and the thesis describes studies carried out on an aldose-ketose isomerase enzyme of the pathway. The biosynthetic origin of β-ethynyl-L-serine is not known. A total synthesis of this acetylenic amino acid is descibed along with the development of a new analytical method for identifying the metabolite and for future isotope-labelling based biosynthetic studies. Chapter 1 presents the background of this research. It is focussed on the biosynthesis of fluoroacetate and 4-fluoro-L-threonine by S. cattleya and it also introduces alkyne-containing natural products and their biosynthesis. Chapter 2 describes the work carried out on crystallisation of the aldose-ketose isomerase of the fluorometabolite pathway in S. cattleya. Crystals of the isomerase were obtained and they were diffracted by X-ray, however a structure could not be solved. Chapter 3 contains site-directed mutagenesis studies of the isomerase from S. cattleya. Chapter 4 describes an enantioselective total synthesis of β-ethynyl-L-serine. A robust analytical technique based on derivatisation using 'Click' chemistry and LC-MS was developed for the detection of this amino acid directly from the fermentation broth. Chapter 5 details the experimental procedures for compounds synthesised in this thesis and the biological procedures for gene cloning and protein purification. | en_US |
dc.language.iso | en | en_US |
dc.publisher | University of St Andrews | |
dc.subject | Streptomyces cattleya | en_US |
dc.subject | Fluorometabolite | en_US |
dc.subject | Organofluorine natural products | en_US |
dc.subject | Isomerase | en_US |
dc.subject | Fluorinase | en_US |
dc.subject | Protein crystallography | en_US |
dc.subject | Ethynylserine | en_US |
dc.subject | Rare amino acids | en_US |
dc.subject | Click chemistry | en_US |
dc.subject | Acetylenic amino acid | en_US |
dc.subject.lcc | QR88.3C5 | |
dc.subject.lcsh | Streptomyces--Metabolism | en_US |
dc.subject.lcsh | Microbiological synthesis | en_US |
dc.subject.lcsh | Toxins--Synthesis | en_US |
dc.subject.lcsh | Amino acids--Synthesis | en_US |
dc.subject.lcsh | Isomerases | en_US |
dc.title | Identification and enzyme studies of rare amino acid biosynthesis from Streptomyces cattleya | en_US |
dc.type | Thesis | en_US |
dc.type.qualificationlevel | Doctoral | en_US |
dc.type.qualificationname | PhD Doctor of Philosophy | en_US |
dc.publisher.institution | The University of St Andrews | en_US |
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